Background:Tobacco smoking is more and more frequently included among the factors influencing the natural history of HCV infection as an independent risk factor for acceleration of morphologic changes in the liver, especially fibrosis,and deterioration of liver function. The problem of tobacco smoke hepatotoxicity is most probably associated with oxidative liver damage by the free radicals it contains.The disturbances of oxidation in the course of iral hepatitis are reflected by abnormal metabolism of glutathione. The aim of the study was to demonstrate the independent, harmful effect of smoking on the progression of the disease in patients with chronic HCV infections. Material/Methods: The questionnaire survey included several hundred patients with chronic HCV,66 of whom were qualified for further analysis. The questionnaires included questions concerning smoking,alcohol consumption,use of drugs and concurrent diseases.Statistical analysis took into account the following questionnaire data and data from the patients ’medical records:sex,age,duration of the infection, infection route,smoking (duration of the habit,number of cigarettes a day), the presence of primary risk factors for progression of hepatic lesions (i.a.alcohol, drugs, other liver diseases), the score of morphologic changes in the liver ALT and iron metabolism parameters (iron,ferritin,TIBC), determined on the date of liver biopsy.Statistical analysis of the data was carried out using the ‘Statistica 5.5 PL ’software package.Results: The analyzed group of 66 patients included:38 smokers:9 women aged 26 –64 (median age 50.3 years)and 29 men aged 30 –72 (median age 49.4 years),and 28 non-smokers: 20 women aged 25 –63 lat (median age 48.9)and 8 men aged 22 –57 (median age 47.5 years).Among the smokers, women had been infected with HCV for 2 –16 years (median 6.7),and men for 2 –31 years (median 11.3).Among the non-smokers, the duration of infection ranged from 2 to 44 years in women (median 13.9),and from 6 to 27 years in men (median 13.2). Women had been smoking for 5 to 40 years (median 25)and smoked on the average 11.6 cigarettes a day (range 6-20/day) and men –16.1 cigarettes a day (range 2 –30/day)for 10 to 45lat (median duration of smoking 26.1 years).No significant differences in sex,age and duration of the disease were observed between the smokers and non-smokers. Men smoked significantly more frequently in comparison with women, but no significant differences between men and women concerning duration of the habit and number of cigarettes smoked were demonstrated. Twenty four subjects in the study group –17 smokers and 7 non-smokers -presented additional risk factors for progression of hepatic lesions (e.g.consumption of alcohol ,use of analgesics, hormonal treatment, sedatives or hypnotics). The putative infection routes included:36 (54.6%)so-called hospital infections,(23 (60.6%)among smokers and 13 (46.4%) among non-smokers),20 cases (30.3%)of transfusion-related hepatitis (10 (26.3%)smokers and 10 (35.7%)non-smokers), 1 (1.5%)infection in an injection drug addict and smoker, 9 (13.6%)so-called occasional infections ,ncluding 4 (10.5%) among smokers and 5 (17.9%)among non-smokers. There were no statistically significant differences with respect to infection routes between smokers and non-smokers. Mean blood serum ALT levels were 196.32 U/l among smokers and 165.75 among non-smokers (p>0.5).Mean serum Fe was 168.85 ug% in smokers and 140.19 ug% in non-smokers (p